Biomedical subjects

Makio Mukai

Publications and source records attributed to Makio Mukai.

At least 37 records · Page 2Linked to original sources

PubMed2005

The mechanism of ring enhancement in hepatocellular carcinoma on superparamagnetic iron oxide-enhanced T1-weighted images: an investigation into peritumoral Kupffer cells.

PURPOSE: To investigate the mechanism of ring enhancement on ferumoxides-enhanced T1-weighted (T1W) gradient echo images in malignant focal hepatic lesions. MATERIALS AND METHODS: Eighteen patients with hepatocellular carcinoma (HCC) underwent breath-hold T1-, T2-, and T2*-weighted magnetic resonance (MR) images at 1.5-Tesla after ferumoxides administration. The existence of ring enhancement on T1W, and the maximum size of the area showing decreased phagocytic activity on T2W and T2*W, and that of the area showing ring enhancement on T1W were evaluated. The Kupffer cell (KC) density of HCC itself and peritumoral liver parenchyma was assessed with KC stain sections. RESULTS: Ring enhancement was noted in 13 of 18 HCC (72%). Peritumoral KC density was increased in the ring enhancement (+) group as compared with the ring enhancement (-) group. In the ring enhancement (+) group, the tumor size measured on T2W was smaller than that measured on either T1W or T2*W, suggesting a sustained T1 relaxation effect and a decreased T2* relaxation effect in the peritumoral regions. CONCLUSION: Ring enhancement on superparamagnetic iron oxide (SPIO)-enhanced T1W may correlate with increased KC density and decreased SPIO clustering in KC in peritumoral regions.

Aged↗

PubMed2005

Credentialing of nuclear medicine physicians, surgeons, and pathologists as a multidisciplinary team for selective sentinel lymphadenectomy.

There are several possible applications of the sentinel lymph node (SLN) concept with different technological aspects such as individualized surgical management of solid tumors, multidisciplinary treatments, and novel therapeutic approaches. To achieve these clinical applications, multidisciplinary teamwork with surgeons, nuclear medicine physicians, and pathologists would be critically required. Interdisciplinary issues should be resolved in order to develop optimal standard procedures of SLN dissection for various solid tumors.

Credentialing↗

PubMed2005

Sentinel lymph node mapping in esophageal and gastric cancer.

In recent years, the sentinel lymph node (SLN) concept has been widely investigated in a variety of solid tumors including gastrointestinal (GI) cancer. This chapter reviews the rationale and refined technical aspects for SLN mapping in upper GI cancer for the intraoperative accurate diagnosis of nodal status to perform individualized minimally invasive surgical approaches. We have described the technical details of the procedure as we have performed it in over 350 consecutive patients with esophageal and gastric cancer and introduced pitfalls and issues remaining. The technical details and clinical applications of SLN mapping differfor patients with esophageal cancer and gastric cancer. Radio-guided method with lymphoscintigraphy using radioisotope-labeled colloid (RI) is essential for SLN mapping for esophageal cancer. Selective lymphadenectomy and SLN-targeted chemoradiotherapy would be feasible and beneficial for the patients with esophageal cancer. For gastric cancer, combined method with dye and RI is recommended for stable and accurate sampling of SLN in the laparoscopic setting. Laparoscopic local resection for superficial gastric cancer with negative SN status would be a reasonable and less-invasive novel procedure based on the SLN concept. We can utilize this procedure not only for an accurate staging but also as a great tool to change the patient care of upper GI cancer by individualized minimally invasive treatments.

Esophageal Neoplasms↗

PubMed2005

A novel apoptosis-inducing monoclonal antibody (anti-LHK) against a cell surface antigen on colon cancer cells.

BACKGROUND: Apoptosis is a crucial element in the behavior of mammalian cells in many different situations. We here report the establishment of a novel monoclonal antibody (anti-LHK mAb) that has apoptosis-inducing activity against colon cancer Colo205 cells. METHODS: The mechanism of anti-LHK mAb-induced cell death was assessed by microscopic morphology, Annexin V/Hoechst 33528 staining, and detection of DNA fragmentation. The molecular weight of LHK antigen was determined by Western blotting. Growth inhibition of Colo205 cells induced by anti-LHK mAb was determined by in vitro and in vivo studies. RESULTS: Anti-LHK reacted with a 70-kDa antigen and completely blocked the proliferation of Colo205 cells bearing LHK in vitro in a manner characteristic of apoptosis. Strikingly, anti-LHK mAb suppressed tumor growth in a murine peritoneal dissemination model. CONCLUSIONS: LHK antigen, which is restricted to epithelial cells, may be a novel death receptor that plays a critical role in controlling the growth, invasion, and metastasis of human colon cancer cells.

Animals↗

PubMed2005

Increasing age does not affect efficacy of sentinel lymph node biopsy using smaller-sized technetium-99m tin colloids for breast cancer patients.

BACKGROUND: Increasing age of breast cancer patients was reported to cause not only failure of sentinel lymph node (SLN) identification but also false negative results. METHODS: A retrospective review was conducted of breast cancer patients who underwent sentinel lymph node biopsy (SLNB) using small-sized technetium-99m-labeled tin colloid (particle size: 200-400 nm in diameter). A comparison between 82 patients who were less than 60 years and 40 patients who were > or =60 years of age was performed to evaluate the efficacy of SLNB using the small-sized tin colloid in older patients. RESULTS: One hundred twenty-two clinically node-negative breast cancer patients underwent SLNB. Apart from age, there were no statistically significant differences between the younger patients and the older patients in terms of the clinicopathologic characteristics. Successful mapping rates, false negative rates, and accuracy were comparable between the 2 groups. CONCLUSIONS: SLNB using the small-sized tin colloid was not affected by increasing age.

Adult↗

PubMed2005

The sealing effect of fibrin glue against alveolar air leakage evaluated up to 48 h; comparison between different methods of application.

OBJECTIVE: There is little experimental evidence to show how much positive airway pressure fibrin sealants can actually withstand, and in particular, how this effect changes over time. In the present study, we experimentally evaluated the sealing effect of fibrin glue against alveolar air leakage up to 48 h after application. METHODS: Beagles were used (n = 48). Under thoracotomy, approximately 5 x 10 mm defects (2 mm depth) were made on the lung surface. Fibrin glue sealants were applied to this defect in three ways. In rubbing and spray method, fibrinogen was rubbed, followed by spraying of both fibrinogen and thrombin solutions. In double layer method, fibrinogen was dripped, followed by thrombin. Collagen fleece, coated with fibrinogen and thrombin (TachoComb) was also tested. The minimum positive airway pressure which produced air leakage was measured for each sealed defect (seal breaking pressure, cmH2O) at 0, 3, 6, 12, 24, and 48 h after application (n = 6 at each time point). RESULTS: The seal-breaking pressure increased over time in all of the application methods. At 6 h, differences between methods were not significant but three defects in RS reached 70 cmH2O, the maximum pressure tested, compared with none in other two methods. At 12h, the seal-breaking pressure was significantly higher in RS compared with the other two methods (rubbing and spray method vs TachoComb; 66+/-3 vs 47+/-17, P = 0.047, rubbing and spray method vs double layer method; 66+/-3 vs 42+/-18, P = 0.024). Beyond 24 h, sealing pressure reached close to 70 cmH2O in all the methods. CONCLUSIONS: The results show that the sealing effect of fibrin glue is relatively unstable up to 12h after its application. Rubbing and spray method may help the fibrin seal to reach its full strength faster compared with the other two methods.

Aerosols↗

PubMed2005

Increase of bone marrow-derived secretory lineage epithelial cells during regeneration in the human intestine.

BACKGROUND & AIMS: We have previously reported that bone marrow (BM)-derived cells contribute to the regeneration of the human intestinal epithelium. To analyze further how these cells arise, proliferate, and differentiate as epithelial cells, histologic analysis was conducted using endoscopic specimens. METHODS: Thirty biopsy specimens from 14 female, sex-mismatched BM-transplantation recipients were examined. BM-derived cells were identified by fluorescent in situ hybridization (FISH) for the Y chromosome and immunohistochemistry. Multicolor FISH was used to exclude cell fusion. These cells were further analyzed for various differentiation or proliferation markers. RESULTS: No evidence of cell fusion was detected. BM-derived cells did not distribute within the crypt as stem cells and rarely expressed Musashi-1. However, BM-derived epithelial cells frequently expressed Ki-67, and some of these cells appeared as pairs of adjacent cells. These cells also expressed markers of all 4 lineages of terminally differentiated cells. During regeneration following graft-vs-host disease, the number of BM-derived cells was substantially increased within Ki-67-positive cells. Interestingly, the number of cells expressing markers for secretory lineage cells was significantly increased within BM-derived cells. This change was unique for BM-derived cells, resulting in a significantly increased proportion of BM-derived cells among secretory lineage cells. CONCLUSIONS: BM-derived epithelial cells arise via a mechanism other than cell fusion and rarely give rise to stem cells. However, a small proportion of these cells express proliferation markers, and a majority reside as terminally differentiated cells. During regeneration BM-derived cells increase as secretory lineage cells, thereby contributing to restore epithelial functions.

Biopsy↗

PubMed2005

Gastric cancer mimicking a submucosal tumor diagnosed by laparoscopic excision biopsy.

We report a case of advanced gastric cancer exhibiting the features of a submucosal tumor (SMT) of the gastric body. The patient was a 50-year-old male in whom a gastric SMT was detected during a mass screening examination. Upper gastrointestinal endoscopy revealed a protuberant tumor, 2 cm in diameter, covered with normal-appearing mucosa. Examination of an endoscopic biopsy specimen of the tumor revealed chronic gastritis with regenerative and erosive changes. An endoscopic ultrasound examination demonstrated a hypoechoic mass in the third layer of the gastric wall. The clinical diagnosis was gastric SMT, and the patient's course was monitored. Twenty-six months after the initial visit to our hospital, an endosonograph-guided biopsy revealed Group III (borderline lesion). Three months after the biopsy, the size of the SMT had increased slightly. Laparoscopic wedge resection of the tumor was performed to make a pathologic diagnosis and we were able to make a diagnosis of gastric lymphoepithelioma-like carcinoma intraoperatively. Gastrectomy with lymph node dissection was followed as curative surgery. Laparoscopic total excision biopsy is a useful technique in patients with a gastric SMT whose diagnosis has not been confirmed pathologically.

Biopsy↗

PubMed2005

C-jun activation in acquired cystic kidney disease and renal cell carcinoma.

PURPOSE: Activator protein-1 has a central role in transducing cytokine signals. Activator protein-1 is composed of 2 proto-oncogene families, namely Jun and Fos. Of them c-Jun has been suggested to have a role in cell cycle progression and neoplastic transformation. We examined the impact of c-Jun protein activation on pathological parameters in renal cell carcinoma (RCC). MATERIALS AND METHODS: The expression of total c-Jun protein and phosphorylated c-Jun protein was determined by immunohistochemistry in 72 patients with RCC, including 10 with tumor arising from acquired cystic kidney disease (ACKD) of end stage kidneys. RESULTS: c-Jun expression was observed in the distal but not the proximal tubules. Atypical hyperplastic cells in ACKD were positive for phosphorylated c-Jun. RCC arising in end stage kidneys was pT1 and 5 of these cases showed increased c-Jun activation. Of 62 cases arising from normally functioning kidneys 21 showed an increased degree of c-Jun activation. In localized small cell cases (pT1a) 55.5% (10 of 18) showed enhanced activation, whereas such enhanced activation was only observed in 25% (11 of 44) of more advanced cases (pT1b or greater). Therefore, c-Jun activation was considered to be related to the early carcinogenesis of RCC. CONCLUSIONS: This study emphasizes the role that c-Jun activation has in early RCC carcinogenesis. Thus, chronic stimulation of cytokines inducing c-Jun activation may have a role in the aberrant proliferation of hyperplastic atypical cells in ACKD and RCC.

Adult↗

PubMed2005

Comparison between in situ hybridization and real-time PCR technique as a means of detecting the integrated form of human papillomavirus 16 in cervical neoplasia.

Integration of the human papillomavirus (HPV) genome is thought to be one of the causes of cancer progression. However, there is controversy concerning the physical status of HPV 16 in premalignant cervical lesions, and there have been no reports on the concordance between detection of the integrated form of HPV16 by real-time PCR and by in situ hybridization. We investigated specimens of cervical intraepithelial neoplasia (CIN) and invasive carcinomas for the physical status of HPV 16 by real-time PCR and in situ hybridization. The presence of the integrated form was detected by both real-time PCR and in situ hybridization in zero of four cases of CIN1, three of six cases of CIN2, nine of 27 cases of CIN3, and two of six cases of invasive carcinomas. Integrated HPV 16 was present in some premalignant lesions but was not always present in carcinomas. The concordance rate between the two methods for the detection of the presence of the integrated form was 37 of 43 (86%) cases. Real-time PCR and in situ hybridization were found to be complementary and convenient techniques for determining the physical status of the HPV genome. We conclude that a combination of both methods is a more reliable means of assessing the physical status of the HPV genome in cervical neoplasia.

Carcinoma↗

PubMed2005

Primary bone carcinosarcoma: chondrosarcoma and squamous cell carcinoma with keratin pearl formation.

Malignant bone tumors with epithelial differentiation are extremely rare. Only one case of primary malignant bone tumor with distinct squamous cell carcinoma and chondrosarcoma has ever been reported. Reported herein is a case of primary malignant bone tumor with distinct squamous cell carcinoma and chondrosarcoma, so-called carcinosarcoma of bone, arising in the femur of a 53-year-old man. The tumor was located within the femur and was diagnosed by curettage as a well-differentiated chondrosarcoma. No primary tumor was detected in any other organ. Within a few months the tumor had rapidly grown toward the soft tissue, and hemipelvectomy was performed. Examination of the surgical specimen revealed that the tumor was mainly composed of undifferentiated spindle sarcoma cells with scattered foci of chondrosarcoma and of squamous cell carcinoma with keratin pearl formation. The patient died approximately 6 months postoperatively. At autopsy multiple metastases were detected in the heart, both lungs, muscles, and lymph nodes. Interestingly, the chondrosarcoma and squamous cell carcinoma components were observed in several metastatic foci. The tumors in both the previously reported case and the present case contained components of chondrosarcoma and squamous cell carcinoma with keratin pearl formation, and this combination of histological features may be a unique characteristic of carcinosarcoma of bone.

Bone Neoplasms↗

PubMed2005

Is laser conization adequate for therapeutic excision of adenocarcinoma in situ of the uterine cervix?

AIMS: To determine the safety of uterine-preserving operations for adenocarcinoma in situ of the cervix. METHODS: Fifteen cases of adenocarcinoma in situ (AIS) were diagnosed using neodymium:yttrium aluminum garnet (Nd:YAG) laser conization. The accuracy of preconization histology or cytology was evaluated in 15 AIS cases. In these AIS cases, we investigated how far the tumor was located from the squamocolumnar junction (SCJ) and the endocervix. Fourteen cases of the 15 AIS-affected patients were treated using laser conization alone. These patients were closely followed up. RESULTS: Precise agreement between preconization diagnosis and conization histology was seen in 46.7% (7/15) of the AIS cases. In 14 of the 15 cases of AIS (93.3%), the tumor was adjacent to the transitional zone, within 3 mm of the SCJ, and in the other case (6.7%), the tumor was between 0 and 5 mm away from the SCJ. In all subjects, cone height was 8-18 mm (mean 13.1 mm). None of the 15 patients showed any recurrence of AIS during follow up ranging from 15 to 75 months (43.1 months on average). CONCLUSIONS: Women with AIS who want to preserve their fecundity might be treated with laser conization alone.

Adenocarcinoma↗

PubMed2005

Basaloid squamous carcinoma of the hypopharynx with an extensive spindle cell component exhibiting a pedunculated polypoid mass.

We report a case of basaloid squamous carcinoma of the hypopharynx with an extensive spindle cell component in an 82-year-old man. The tumor (4.0 x 2.5 x 2.2 cm) was a pedunculated polypoid mass that was attached to the left pyriform sinus. Histologically, most (70%) of the tumor was composed of malignant spindle cell proliferation, and the rest (30%) was basaloid squamous carcinoma. Some of the spindle cells were positive for cytokeratins. The preoperative histologic diagnosis was difficult because the endoscopic biopsy specimens showed only spindle cell proliferation. This is an unusual presentation of basaloid squamous carcinoma of the head and neck.

Aged↗

PubMed2004

HMMC-1: a humanized monoclonal antibody with therapeutic potential against Müllerian duct-related carcinomas.

PURPOSE: The purpose of this research was to generate a human monoclonal antibody specific to gynecological cancers and to evaluate such an antibody as therapy for gynecological cancers. EXPERIMENTAL DESIGN: Transchromosomal KM mice were immunized with the human uterine endometrial cancer cell line SNG-S. Hybridomas were constructed between spleen cells from KM mice and mouse myeloma cells. Reactivity of the antibody was evaluated by immunohistochemistry of pathological specimens of gynecological cancers. Cytotoxicity of HMMC-1 against SNG-S cells was tested by in vitro cytotoxicity assays. The epitope of HMMC-1 was determined by transfection with a panel of glycosyltransferase cDNAs and by inhibition assays with chemically synthesized oligosaccharides. RESULTS: HMMC-1 is a human IgM monoclonal antibody that reacts positively with mullerian duct-related carcinomas with positive rates of 54.6% against uterine endometrial adenocarcinoma, 76.9% against uterine cervical adenocarcinoma, and 75.0% against epithelial ovarian cancer. HMMC-1 does not react with normal endometrium at proliferative or secretory phases, normal uterine cervix, or normal and malignant tissue from other organs, whereas it reacts weakly with the epithelium of the gall bladder and the collecting duct of the kidney. HMMC-1 exhibits antigen-dependent and complement-mediated cytotoxicity. Upon cotransfection with cDNAs encoding two glycosyltransferases required for fucosylated extended core 1 O-glycan, mammalian cells express HMMC-1 antigen. Finally, binding of HMMC-1 to SNG-S cells is inhibited by synthetic Fucalpha1-->2Galbeta1-->4GlcNAcbeta1-->3Galbeta1-->3GalNAcalpha1-octyl. CONCLUSIONS: These results indicate that HMMC-1 specifically recognizes a novel O-glycan structure. The unique specificity and cytotoxicity of HMMC-1 strongly suggest a therapeutic potential of this antibody.

Animals↗

PubMed2004

Comparison of K-ras point mutation distributions in intraductal papillary-mucinous tumors and ductal adenocarcinoma of the pancreas.

Intraductal papillary-mucinous tumors (IPMT) consist of cells with varying histologic degrees of severity and exhibit multiple tumor loci; however, whether or not these lesions exhibit the same genetic changes has not been clarified. To investigate this point, we analyzed K-ras mutations in multiple IPMT lesions from each patient enrolled in our study and compared our findings to those for patients with ductal adenocarcinoma of the pancreas (DC). Twenty IPMT specimens and 7 DC specimens were resected, microdissected and analyzed for the presence of K-ras mutations. The mutated genes were then sequenced using a genetic analyzer. K-ras mutations were observed in 80% of IPMT and 100% of DC patients. More than 2 types of K-ras mutation were observed in the main tumors of 43.8% of IPMT and 0% of DC patients. K-ras mutations in peritumoral and separated lesions were observed in 66.7% and 62.5% of IPMT patients, respectively. At least one identical mutation between the main tumor and the peritumoral or separated lesions was recognized in all of the IPMT patients with those lesions. Different mutations from those in the main tumor were observed in 40% of IPMT patients with separated lesions. The survival curve of IPMT-carcinoma patients with more than 2 types of K-ras mutation in the main tumor was better than that with one type of K-ras mutation. IPMT patients exhibit a remarkably genetic heterogeneity in main tumor and have good prognosis.

Adenocarcinoma↗

PubMed2004

Current status and future prospects of sentinel node navigational surgery for gastrointestinal cancers.

Until the late 1990s, the application of the sentinel node (SN) concept to gastrointestinal (GI) malignancies was not recognized because of the multidirectional and complicated lymphatic flow from the GI tract. However, several studies supporting the validity of the SN concept for GI cancers have been reported in the past 5 years. Because of its anatomical location, gastric cancer is one of the most suitable targets for minimally invasive surgery based on SN status. Laparoscopic local resection is theoretically feasible for curative treatment of SN-negative early gastric cancer. Although SNs in esophageal cancer are multiple and are distributed widely from the cervical to the abdominal area, selective and modified lymphadenectomy for clinically N0-stage esophageal cancer is likely to become feasible and clinically viable. Total mesorectal excision (TME) is accepted as a standard surgical procedure for rectal cancer. However, there is a risk of aberrant distribution of SNs beyond the extent of TME; for example, SNs may be lateral to the lower rectum. SN mapping with scintigraphy is useful for effective sampling of SNs in unexpected areas and accurate staging without extensive lymph node dissection. There are several practical issues to be overcome. The techniques and feasibility of laparoscopic SN sampling are still under investigation. Large-scale multicenter prospective validation studies for SN mapping in GI cancer are essential. If these remaining issues can be solved, SN mapping for GI cancer will have great clinical impact.

Biliary Tract Neoplasms↗

PubMed2004

Significance of metastasis detected by molecular techniques in sentinel nodes of patients with gastrointestinal cancer.

The clinical significance of micrometastasis in sentinel nodes (SNs) may differ in various organs. In particular, the prognostic value of SN micrometastases detected by reverse transcriptase-polymerase chain reaction (RT-PCR) is still controversial. We investigated the diagnostic and therapeutic significance of nodal molecular metastasis detected by nested RT-PCR for cytokeratin (CK) 19 mRNA in gastrointestinal cancer. In 51 cases with GI tract cancer treated by standard curative resection, SNs were identified by a radio-guided method. In 10 of 51 patients, 25 SNs and 3 non-SNs were histologically negative and RT-PCR positive. Three non-SNs with positive CK19 mRNA were randomly sampled from the same basin where histologically positive SNs were identified. Immunohistochemical analysis of six additional step sections obtained at 30- micro m intervals with use of an anticytokeratin antibody showed clearly recognizable histological metastases in 4 of 25 histologically negative/RT-PCR-positive SNs (16%). In one case of esophageal squamous cell carcinoma with nodal micrometastasis identified by CK19 RT-PCR, extranodal local recurrence in the SN basin (left supraclavicular basin) was observed 6 months postoperatively. These findings suggest that nodal micrometastasis detected by nested RT-PCR has some clinical significance in GI cancer. Molecular assessment of the SN may be a valuable tool to complement routine histological examination for GI cancers.

Esophageal Neoplasms↗

PubMed2004

Effects of preinjury administration of corticosteroids on pseudointimal hyperplasia and cytokine response in a rat model of balloon aortic injury.

Restenosis occurs in approximately one-third of patients with coronary or peripheral vascular disease who undergo balloon angioplasty or a surgical bypass procedure primarily because of the development of pseudointimal hyperplasia (PIH). Corticosteroids were effective in suppressing PIH in several experimental studies, but no clinical studies have been reported. To resolve this discrepancy, we studied the effects of preinjury administration of several doses of methylprednisolone (MP) at targeted times in a rat model of balloon aortic injury. Rats were given either no treatment or an intravenous injection of MP (0.5, 5.0, 50, or 500 mg/kg) 2 hours before aortic injury. Four hours later interleukin-6 (IL-6), IL-10, and macrophage migration inhibitory factor (MIF) concentrations in serum and tissue of injured aortas were assessed. Two weeks after injury, damaged aortas were harvested and studied histopathologically. Compared with results in controls, MP at a dose of 5 mg/kg significantly inhibited increases in plasma and tissue levels of IL-6 and significantly reduced the pseudointimal area, pseudointimal/medial area ratio, and proliferating cell nuclear antigen index in injured vessels. Administration of MP had no significant effect on the IL-10 or MIF level. Thus in a rat model of balloon aortic injury, preinjury administration of MP 5 mg/kg mitigated the development of PIH and cell proliferation and suppressed the postinjury increase in serum and tissue IL-6 concentrations. These results suggest that there is an appropriate dosage as well as appropriate timing for MP administration to suppress PIH.

Angioplasty, Balloon↗